U.S. patent application number 10/364236 was filed with the patent office on 2003-11-20 for microstructure fabrication and microsystem integration.
Invention is credited to Huang, Zhili.
Application Number | 20030214057 10/364236 |
Document ID | / |
Family ID | 34192913 |
Filed Date | 2003-11-20 |
United States Patent
Application |
20030214057 |
Kind Code |
A1 |
Huang, Zhili |
November 20, 2003 |
Microstructure fabrication and microsystem integration
Abstract
Fabrication of a microstructure device includes assembling a
mold component and a mold body to form a device mold for the
microstructure device. The microstructure device is cast from the
device mold, then the mold component is removed from the
microstructure device. The microstructure device is then released
from the mold body.
Inventors: |
Huang, Zhili; (Plainsboro,
NJ) |
Correspondence
Address: |
FISH & RICHARDSON PC
225 FRANKLIN ST
BOSTON
MA
02110
US
|
Family ID: |
34192913 |
Appl. No.: |
10/364236 |
Filed: |
February 11, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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60380607 |
May 15, 2002 |
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Current U.S.
Class: |
264/1.1 ;
264/2.5; 425/808 |
Current CPC
Class: |
B01J 2219/00873
20130101; B01L 3/502715 20130101; B33Y 80/00 20141201; G01N
27/44721 20130101; B01J 2219/00833 20130101; B01L 2300/0816
20130101; B01J 2219/00783 20130101; B01J 2219/0095 20130101; B01L
3/50273 20130101; B29C 39/34 20130101; B01L 2200/027 20130101; B29C
39/36 20130101; B29C 33/0033 20130101; B29L 2011/0016 20130101;
B29L 2011/0075 20130101; B01L 3/502707 20130101; B29C 33/3842
20130101; B01L 2300/1827 20130101; G01N 27/44791 20130101; B29C
33/52 20130101; B01J 19/0093 20130101; B29C 39/10 20130101; B29L
2031/3406 20130101; B01J 2219/0097 20130101; B01L 2400/0481
20130101; B01L 2200/12 20130101; B01L 2300/0654 20130101 |
Class at
Publication: |
264/1.1 ;
264/2.5; 425/808 |
International
Class: |
B29D 011/00 |
Claims
What is claimed is:
1. A method of fabricating a microstructure device, comprising:
assembling a mold component and a mold body to form a device mold
for the microstructure device; casting the microstructure device
from the device mold; removing the mold component from the
microstructure device; and releasing the microstructure device from
the mold body.
2. The method of claim 1 wherein casting the microstructure device
comprises pouring or injecting a liquid polymer into the device
mold.
3. The method of claim 2, further comprising combining the liquid
polymer with a filler material or reinforcement particles.
4. The method of claim 2 wherein the liquid polymer comprises
polyurethane, polydimethylsiloxane, polycarbonate, polypyrrole,
resin, Teflon resin, epoxy, polymeric rubber, or polymeric
plastic.
5. The method of claim 1 wherein the mold component comprises wax,
gel, fusible alloy, eutectic alloy, resin, lipid, or ammonium
salt.
6. The method of claim 1 wherein the mold component has structures
having a dimension less than 5 millimeters.
7. The method of claim 1 wherein the mold component comprises a
reversible material that changes from a solid form to a liquid form
or from a liquid Finn to a solid form depending on changes in one
or more environment conditions.
8. The method of claim 7 wherein removing the mold component
comprises changing the one or more environment conditions so that
the reversible mold component changes from a solid form to a liquid
form.
9. The method of claim 7 wherein removing the mold component
comprises applying a centrifugal force to draw the mold component
in liquid form away from the microstructure device.
10. The method of claim 7 wherein removing the mold component
comprises using a suction force to draw the mold component in
liquid form away from the microstructure device.
11. The method of claim 1 wherein the mold component comprises a
material that changes from a solid form to a gaseous form or from a
gaseous form to a solid form depending on changes in one or more
environment conditions.
12. The method of claim 11 wherein removing the mold component
comprises changing the one or more environment conditions so that
the mold component changes from a solid form to a gaseous form.
13. The method of claim 1 wherein the mold component comprises a
soluble material that can be cast into a predefined shape as
defined by a mold and later be dissolved in a solvent.
14. The method of claim 13 wherein removing the mold component
comprises flushing the mold component out from the microstructure
device with a solvent that dissolves the mold component.
15. The method of claim 1 wherein the mold component has a shape
that is complementary of a structure of the microstructure device
after the mold component is removed from the microstructure
device.
16. The method of claim 1 wherein the mold component comprises an
elongated mold component having a same dimension and shape as a
channel in the microstructure device after the mold component is
removed from the microstructure device.
17. The method of claim 1, further comprising fabricating the mold
component by using a component mold.
18. The method of claim 17 wherein fabricating the mold component
comprises pouring a material in a liquid form into the component
mold, and changing one or more environment conditions so that the
material changes to a solid or gel form.
19. The method of claim 17 wherein the component mold has a cavity
having a shape that is substantially the same as a shape of the
mold component, the cavity being connected to an exterior of the
component mold through an opening, wherein fabricating the mold
component comprises injecting a material in a liquid form into the
cavity through the opening, and changing one or more environment
conditions so that the material changes to a solid or gel form.
20. The method of claim 17, wherein the component mold has a cavity
having a shape that is substantially the same as a shape of the
mold component, wherein fabricating the mold component comprises
compressing a material in powder form into the cavity to form the
mold component.
21. A method, comprising: assembling a set of mold components and a
mold body to form a device mold for a microstructure device;
casting the microstructure device from the device mold; and
removing the set of mold components from the microstructure
device.
22. The method of claim 21 wherein casting the microstructure
device comprises pouring or injecting a liquid polymer into the
device mold.
23. The method of claim 21 wherein the set of mold components
includes a first mold component and a second mold component, the
first mold component having a shape configured so that a first
chamber is formed in the microstructure device when the first mold
component is removed from the microstructure device, the second
mold component having a shape configured so that a second chamber
is formed in the microstructure device when the second mold
component is removed from the microstructure device.
24. The method of claim 23 wherein the first and second mold
components are spaced at a distance when the device mold is
assembled so that a flexible membrane is formed in the
microstructure device between the first and second chambers when
the first and second mold components are removed from the
microstructure device.
25. The method of claim 21 wherein the set of mold components
comprises a first elongated mold component and a second elongated
mold component, the first elongated mold component having a
diameter or dimension smaller than the second elongated mold
component, the second elongated mold component having an opening
which has same dimension as the cross section of the first
elongated mold component, and assembling the device mold comprises
inserting the first elongated mold component through the opening in
the second elongated mold component to form an intersection.
26. The method of claim 21, wherein the set of mold components
comprises an elongated mold component and a cylinder, the cylinder
having a passageway with a dimension substantially the same as a
dimension of the elongated mold component, and assembling the
device mold comprises partially inserting the elongated mold
component into the passageway.
27. The method of claim 21 wherein the set of mold components
comprises a castable mold component and an elongated mold
component, the castable mold component having a shape configured to
form a cavity in the microstructure device, the elongated mold
component having a shape configured to form a channel in the
microstructure device, the castable mold component having a recess
structure for receiving an end of the elongated mold component, the
recess structure having means to prevent the castable mold
component from moving relative to the elongated mold member when
the device mold is assembled.
28. The method of claim 27 wherein the elongated mold component has
a first end and a second end, the mold body having a side wall with
a hole, wherein assembling the device mold comprises inserting the
first end of the elongated mold component into the recess structure
of the castable mold component, and inserting the second end of the
elongated mold component through the hole of the side wall of the
device mold.
29. The method of claim 27 wherein the set of mold components
includes a castable mold component having a shape suitable for
forming a cavity and an elongated mold component suitable for
forming a channel connecting the cavity in the microstructure
device, wherein assembling the device mold comprises inserting the
elongated mold component through a hole positioned on a side wall
of the mold body, the elongated mold component supporting and
aligning the castable mold component at a predefined position
relative to the mold body.
30. The method of claim 21 wherein the set of mold components
comprises a post and a mold component, the post supporting the mold
component at a predetermined position relative to the mold body
when the device mold is assembled.
31. A method of fabricating a microstructure device, comprising:
fabricating a device mold by connecting a set of mold components
and to mold body and connecting a set of functional components to
the mold body; casting the microstructure device from the device
mold; and removing the set of mold components from the
microstructure device while retaining the functional components in
the microstructure device.
32. The method of claim 31 wherein casting the microstructure
device comprises pouring or injecting a liquid polymer into the
device mold.
33. The method of claim 31 wherein the set of mold components
comprises a castable mold component, the set of functional
components comprises an electrode having a tip, wherein fabricating
the device mold comprises embedding a tip of the electrode into one
of the castable mold components so that the tip of the electrode is
surrounded by the castable mold component, wherein removing the
castable mold component from the microstructure device exposes the
tip of the electrode to a cavity in the microstructure device.
34. The method of claim 31, wherein the set of mold components
comprises an elongated mold component, the set of functional
components comprises an electrode having a structure that defines a
hole, wherein fabricating the device mold comprises inserting the
elongated mold component through the hole in the electrode.
35. The method of claim 31 wherein the set of mold components
comprises a mold component that defines a conduit in the
microstructure device, the method further comprising coating a
surface of the conduit with a material having a refractive index
lower than a refractive index of a liquid material used for filling
the conduit.
36. An apparatus, comprising: a microdevice body having a structure
that defines a channel to allow passage of a fluid; an electrical
component to interact with a portion of the liquid, a portion of
the electrical component being embedded in the microdevice body;
and an optical component to generate, transmit, or receive light
that interacts with a portion of the liquid, a portion of the
optical component being embedded in the microdevice body such that
the microdevice body and the optical component and the electrical
component form an integrated unit.
37. The apparatus of claim 36 in which the microdevice body is
substantially made of polymer.
38. The apparatus of claim 36, further comprising a platform for
supporting the electrical component and the optical component at
predetermined positions.
39. The apparatus of claim 38, wherein the platform comprises a
circuit board.
40. The apparatus of claim 36, further comprising a device mold for
casting the microdevice body.
41. The apparatus of claim 36, further comprising a controller that
is integrated with the microdevice body to control the electrical
component.
42. The apparatus of claim 41 in which the structure of the
microdevice body further defines a chamber connected to the
channel, the electrical component comprising a heater integrated
with the microdevice body for heating a liquid in the chamber, the
heater being controlled by the controller.
43. The apparatus of claim 42 in which the microcontroller controls
the heater to heat the liquid in the chamber according to a
predefined protocol to facilitate a polymerase chain reaction.
44. The apparatus of claim 36 in which the optical component
comprises an optical waveguide.
45. The apparatus of claim 36 in which the optical component
comprises a photo sensor.
46. The apparatus of claim 36 in which the structure of the
microdevice body further defines a chamber, and the apparatus
further comprising a valve to open or close the channel, the valve
comprising a diaphragm made of shape memory alloy.
47. The apparatus of claim 36 in which the structure of the
microdevice body further defines a fluid inlet, a chamber, and an
opening between the fluid inlet and the chamber, the fluid inlet
having a shape such that a fluidic pressure in a direction from the
inlet towards the chamber tends to cause the opening to remain
open, whereas a fluidic pressure in a direction from the chamber
towards the inlet tends to close the opening.
48. The apparatus of claim 36 in which the structure of the
microdevice body further defines a fluid inlet and a chamber, the
fluid inlet has a funnel shape that extends into the chamber, the
fluid inlet and the chamber being separated by a flexible membrane
having a funnel shape having a larger opening that tapers into a
smaller opening that connects the fluid inlet to the chamber.
49. A microfluidic system comprising: a microfluidic device having
fluidic components; and a cassette having interfaces for
interfacing the fluidic components.
50. The apparatus of claim 49 in which the microfluidic device
comprises pneumatic components.
51. The apparatus of claim 50, wherein the cassette comprises
pneumatic interfaces configured to be coupled to the pneumatic
components in the microfluidic device.
52. The apparatus of claim 50 in which the microfluidic device
comprises electrical components.
53. The apparatus of claim 52, wherein the cassette further
comprising electrical interfaces configured to be coupled to the
electrical components in the microfluidic device.
54. An apparatus, comprising: a device mold that includes a mold
body, removable mold components, and functional components, the
mold body and the removable mold components and the functional
components being connected to define a space within the device mold
for casting a microstructure device, the removable components
comprising material that can be removed from the microstructure
device after the microstructure device is cast, the functional
components being integrated with the microstructure device after
the microstructure device is cast.
55. The apparatus of claim 54 wherein the removable mold components
comprise a first set of mold components and a second set of mold
components, the first set of mold component having shapes
configured to form chambers when the first set of mold component
are removed from the microstructure device, the second set of mold
components having shape configured to form channels when the second
set of mold components are removed from the microstructure device,
the first and second sets of mold components being positioned
relative to one another when connected to form the device mold such
that the chambers and channels in combination form a component of a
peristaltic pump.
56. The method of claim 54 wherein the mold body comprises a bottom
wall and a side wall, the side wall defining a hole that is
positioned at a predetermined distance from the bottom wall, the
hole receiving an end of one of the removable mold components, the
predetermined distance selected so that the removable mold
component is disposed at a predefined position relative to the mold
body within the device mold.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent
Application Serial No. 60/380,607 by Zhili Huang entitled
"MICROSTRUCTURE FABRICATION AND SYSTEM INTEGRATION," filed May 15,
2002.
TECHNICAL FIELD
[0002] This invention relates to microstructure fabrication and
microsystem integration.
BACKGROUND
[0003] A micro total analysis system (".mu.Tas", also called a
lab-on-a-chip system) integrates microfluidics components with
microelectromechanical systems (MEMS) into a single miniaturized
device. The micro total analysis system can be used to perform
chemical and biological analyses, such as capillary electrophoresis
(CE), flow cytometry, liquid chromatography (LC), and mass
spectroscopy (MS). The micro total analysis system can also be used
to synthesize chemicals and drugs, and carry out clinical analyses.
The micro total analysis system includes microfluidic devices that
are used to manipulate and analyze fluid samples. Examples of
microfluidic devices include microchannels, microvalves,
micropumps, and micromixers. Because the components of the .mu.Tas
are integrated together, only small amounts of fluid and sample are
required for the analyses. This improves system performance and
reduces sample, reagent, and analysis costs.
SUMMARY
[0004] In general, in one aspect, the invention features a method
of fabricating a microstructure device, including assembling a mold
component and a mold body to form a device mold for the
microstructure device, casting the microstructure device from the
device mold, removing the mold component from the microstructure
device, and releasing the microstructure device from the mold
body.
[0005] Embodiments of the invention may include one or more of the
following features. Casting the microstructure device comprises
pouring or injecting a liquid polymer into the device mold. The
method may include combining the liquid polymer with a filler
material or reinforcement particles. The liquid polymer may include
polyurethane, polydimethylsiloxane, polycarbonate, polypyrrole,
resin, Teflon resin, epoxy, polymeric rubber, or polymeric
plastic.
[0006] The mold component may include a reversible material that
changes from a solid form to a liquid form or from a liquid form to
a solid form depending on changes in one or more environment
conditions. Removing the mold component may include changing the
one or more environment conditions so that the reversible mold
component changes from a solid form to a liquid form. Removing the
mold component may include applying a centrifugal force to draw the
mold component in liquid form away from the microstructure device.
Removing the mold component may include using a suction force to
draw the mold component in liquid form away from the microstructure
device.
[0007] The mold component may include a material that changes from
a solid form to a gaseous form or from a gaseous form to a solid
Finn depending on changes in one or more environment conditions.
Removing the mold component may include changing the one or more
environment conditions so that the mold component changes from a
solid form to a gaseous form. The mold component may include a
soluble material that can be cast into a predefined shape as
defined by a mold and later be dissolved in a solvent. Removing the
mold component may include flushing the mold component out from the
microstructure device with a solvent that dissolves the mold
component.
[0008] The mold component may include wax, gel, fusible alloy,
eutectic alloy, resin, lipid, or ammonium salt. The mold component
may have structures having a dimension less than 5 millimeters. The
mold component may have a shape that is complementary of a
structure of the microstructure device after the mold component is
removed from the microstructure device. The mold component may
include an elongated mold component having a same dimension and
shape as a channel in the microstructure device after the mold
component is removed from the microstructure device.
[0009] The method may include fabricating the mold component by
using a component mold. Fabricating the mold component may include
pouring a material in a liquid form into the component mold, and
changing one or more environment conditions so that the material
changes to a solid or gel form. The component mold may have a
cavity having a shape that is substantially the same as a shape of
the mold component, the cavity being connected to an exterior of
the component mold through an opening, wherein fabricating the mold
component may include injecting a material in a liquid form into
the cavity through the opening, and changing one or more
environment conditions so that the material changes to a solid or
gel form. The component mold may have a cavity having a shape that
is substantially the same as a shape of the mold component, wherein
fabricating the mold component may include compressing a material
in powder form into the cavity to form the mold component.
[0010] In general, in another aspect, the invention features a
method that includes assembling a set of mold components and a mold
body to form a device mold for a microstructure device, casting the
microstructure device from the device mold, and removing the set of
mold components from the microstructure device.
[0011] Embodiments of the invention may include one or more of the
following features. Casting the microstructure device may include
pouring or injecting a liquid polymer into the device mold. The set
of mold components may include a first mold component and a second
mold component, the first mold component having a shape configured
so that a first chamber is formed in the microstructure device when
the first mold component is removed from the microstructure device,
the second mold component having a shape configured so that a
second chamber is formed in the microstructure device when the
second mold component is removed from the microstructure device.
The first and second mold components may be spaced at a distance
when the device mold is assembled so that a flexible membrane is
formed in the microstructure device between the first and second
chambers when the first and second mold components are removed from
the microstructure device.
[0012] The set of mold components may include a first elongated
mold component and a second elongated mold component, the first
elongated mold component having a diameter or dimension smaller
than the second elongated mold component, the second elongated mold
component having an opening which has same dimension as the cross
section of the first elongated mold component, and assembling the
device mold may include inserting the first elongated mold
component through the opening in the second elongated mold
component to form an intersection.
[0013] The set of mold components may include an elongated mold
component and a cylinder, the cylinder having a passageway with a
dimension substantially the same as a dimension of the elongated
mold component, and assembling the device mold may include
partially inserting the elongated mold component into the
passageway.
[0014] The set of mold components may include a castable mold
component and an elongated mold component, the castable mold
component having a shape configured to form a cavity in the
microstructure device, the elongated mold component having a shape
configured to form a channel in the microstructure device, the
castable mold component having a recess structure for receiving an
end of the elongated mold component, the recess structure having
means to prevent the castable mold component from moving relative
to the elongated mold member when the device mold is assembled.
[0015] The elongated mold component may have a first end and a
second end, the mold body having a side wall with a hole, wherein
assembling the device mold may include inserting the first end of
the elongated mold component into the recess structure of the
castable mold component, and inserting the second end of the
elongated mold component through the hole of the side wall of the
device mold.
[0016] The set of mold components may include a castable mold
component having a shape suitable for forming a cavity and an
elongated mold component suitable for forming a channel connecting
the cavity in the microstructure device, wherein assembling the
device mold may include inserting the elongated mold component
through a hole positioned on a side wall of the mold body, the
elongated mold component supporting and aligning the castable mold
component at a predefined position relative to the mold body.
[0017] The set of mold components may include a post and an
elongated mold component, the post supporting the elongated
component at a predetermined position relative to the mold body
when the device mold is assembled.
[0018] In general, in another aspect, the invention features a
method of fabricating a microstructure device. The method includes
fabricating a device mold by connecting a set of mold components
and to mold body and connecting a set of functional components to
the mold body, casting the microstructure device from the device
mold, and removing the set of mold components from the
microstructure device while retaining the functional components in
the microstructure device.
[0019] Embodiments of the invention may include one or more of the
following features. Casting the microstructure device may include
pouring or injecting a liquid polymer into the device mold. The set
of mold components may include a castable mold component, the set
of functional components may include an electrode having a tip,
wherein fabricating the device mold may include embedding a tip of
the electrode into one of the castable mold components so that the
tip of the electrode is surrounded by the castable mold component,
and wherein removing the castable mold component from the
microstructure device exposes the tip of the electrode to a cavity
in the microstructure device.
[0020] The set of castable mold components may include an elongated
mold component, the set of functional components may include an
electrode having a structure that defines a hole, wherein
fabricating the device mold may include inserting the elongated
mold component through the hole in the electrode. The set of mold
components may include an elongated mold component that defines a
conduit in the microstructure device, the method further including
coating a surface of the conduit with a material having a
refractive index lower than a refractive index of a liquid material
used for filling the conduit.
[0021] In general, in another aspect, the invention features an
apparatus that includes a microdevice body having a structure that
defines a channel to allow passage of a fluid, an electrical
component to interact with a portion of the liquid, a portion of
the electrical component being embedded in the microdevice body,
and an optical component to generate, transmit, or receive light
that interacts with a portion of the liquid, a portion of the
optical component being embedded in the microdevice body such that
the microdevice body and the optical component and the electrical
component form an integrated unit.
[0022] Embodiments of the invention may include one or more of the
following features. The microdevice body may be substantially made
of polymer. The apparatus may include a platform for supporting the
electrical component and the optical component at predetermined
positions. The platform may include a circuit board. The apparatus
may include a device mold for casting the microdevice body. The
apparatus may include a controller that is integrated with the
microdevice body to control the electrical component.
[0023] The structure of the microdevice body may define a chamber
connected to the channel, the electrical component may include a
heater integrated with the microdevice body for heating a liquid in
the chamber, the heater being controlled by the controller. The
microcontroller may control the heater to heat the liquid in the
chamber according to a predefined protocol to facilitate a
polymerase chain reaction.
[0024] The optical component may include an optical waveguide. The
optical component may include an optical sensor. The structure of
the microdevice body may define a chamber, and the apparatus may
include a valve to open or close the channel, the valve including a
diaphragm made of shape memory alloy.
[0025] The structure of the microdevice body may define a fluid
inlet, a chamber, and an opening between the fluid inlet and the
chamber, the fluid inlet having a shape such that a fluidic
pressure in a direction from the inlet towards the chamber tends to
cause the opening to remain open, whereas a fluidic pressure in a
direction from the chamber towards the inlet tends to close the
opening.
[0026] The structure of the microdevice body may define a fluid
inlet and a chamber, the fluid inlet has a funnel shape that
extends into the chamber, the fluid inlet and the chamber being
separated by a flexible membrane having a funnel shape having a
larger opening that tapers into a smaller opening that connects the
fluid inlet to the chamber.
[0027] In general, in another aspect, the invention features a
microfluidic system that includes a microfluidic device having
fluidic components, and a cassette having interfaces for
interfacing the fluidic components.
[0028] Embodiments of the invention may include one or more of the
following features. The microfluidic device may include pneumatic
components. The cassette may include pneumatic interfaces
configured to be coupled to the pneumatic components in the
microfluidic device. The microfluidic device may include electrical
components. The cassette may include electrical interfaces
configured to be coupled to the electrical components in the
microfluidic device.
[0029] In general, in another aspect, the invention features an
apparatus that includes a device mold that includes a mold body,
removable mold components, and functional components, the mold body
and the removable mold components and the functional components
being connected to define a space within the device mold for
casting a microstructure device, the removable components including
material that can be removed from the microstructure device after
the microstructure device is cast, the functional components being
integrated with the microstructure device after the microstructure
device is cast.
[0030] Embodiments of the invention may include one or more of the
following features. The removable mold components may include a
first set of mold components and a second set of mold components,
the first set of mold component having shapes configured to form
chambers when the first set of mold component are removed from the
microstructure device, the second set of mold components having
shape configured to form channels when the second set of mold
components are removed from the microstructure device, the first
and second sets of mold components being positioned relative to one
another when connected to form the device mold such that the
chambers and channels in combination form a component of a
peristaltic pump.
[0031] The mold body may include a bottom wall and a side wall, the
side wall defining a hole that is positioned at a predetermined
distance from the bottom wall, the hole receiving an end of one of
the removable mold components, the predetermined distance selected
so that the removable mold component is disposed at a predefined
position relative to the mold body within the device mold.
[0032] Other features, objects, and advantages of the invention
will be apparent from the description and drawings, and from the
claims.
DESCRIPTION OF DRAWINGS
[0033] FIG. 1 shows a perspective view of a multi-chamber
microdevice.
[0034] FIG. 2 shows a front view of the multi-chamber
microdevice.
[0035] FIG. 3 shows a top view of a device mold used to cast the
multi-chamber microdevice.
[0036] FIG. 4 shows a cross sectional views of the device mold used
to cast the multi-chamber microdevice.
[0037] FIG. 5 shows a perspective view of a mold component used in
the device mold.
[0038] FIG. 6 shows top views of a component mold used to cast the
mold component of FIG. 5.
[0039] FIGS. 7 and 8 show cross sectional views of the component
mold.
[0040] FIG. 9 shows a perspective view of a multi-channel
microdevice.
[0041] FIG. 10 shows a top view of a device mold used to cast the
multi-channel microdevice of FIG. 9.
[0042] FIGS. 11-12 show cross sectional views of the device
mold.
[0043] FIG. 13 shows an exploded view of a microfluidic system.
[0044] FIG. 14 shows a top view of the microfluidic device.
[0045] FIG. 15 shows a platform that includes a circuit board and
function components.
[0046] FIG. 16 shows a process for fabricating microstructures in
the microfluidic device.
[0047] FIG. 17 shows a sample loading reservoir.
[0048] FIG. 18 shows a cross sectional view of a peristaltic
micropump.
[0049] FIG. 19 shows a cross sectional view of a microvalve.
[0050] FIG. 20 shows a cross sectional view of an embedded
reservoir integrated with an electrode and two channels.
[0051] FIG. 21 shows a portion of a device mold used to fabrication
the microstructure of FIG. 20.
[0052] FIG. 22 shows electrodes used for electrochemical
detection.
[0053] FIG. 23 shows an electrode.
[0054] FIG. 24 shows microstructures for laser induced fluorescence
detection.
[0055] FIG. 25 shows a cassette having electrical, optical, and
fluidic interfaces for the microfluidic device of FIG. 14.
DETAILED DESCRIPTION
[0056] The following definitions will be used in the description
below:
[0057] The term "reversible material" refers to a material that is
in solid state at a certain temperature, but changes to liquid
state upon changes in the environment condition(s), such as when
heated. The liquid state reversible material changes back to solid
state when the environment condition(s) change in reverse
direction, such as when the temperature lowers back to a certain
degree. Examples of reversible materials are gel, fusible alloy,
eutectic alloy, and resin.
[0058] The term "soluble material" refers to a lipid material that
is in solid state at room temperature, but is soluble when upon
contact with a solvent. Examples of soluble materials are soap,
wax, sterols, and triglycerides.
[0059] The term "sublimable material" refers to a material that is
in solid state at a certain temperature, but changes to vapor upon
changes in the environment condition(s), such as when heated or
when the environment pressure is reduced. The vapor state
reversible material changes back to solid state (usually in powder
form) when the environment condition(s) change in reverse
direction, such as when the temperature lowers back to a certain
degree. An example of sublimable material is ammonium salt, such as
ammonium chloride (NH.sub.4Cl) that completely decomposes into
ammonia (NH.sub.3) and hydrogen chloride (HCl) at 30.degree. C. and
1.3 mbar.
[0060] The term "castable mold component" refers to a mold
component made from one or more reversible, soluble, or sublimable
materials. A castable mold component is molded to a certain shape
that is a complementary of a microstructure to be fabricated inside
a microfluidic device. A castable mold component can be removed
from the microfluidic device after the microfluidic device is
fabricated.
[0061] The term "elongated mold component" refers to a mold
component having an elongated shape, such as a wire, a rod, or a
sheet. A sheet may have a high aspect ratio in which the width and
length are larger than the thickness. An elongated mold component
can be made from steel, plastic, or silicon. An elongated mold
component can also be a castable mold component that is cast from a
mold having an elongated inner cavity.
[0062] FIGS. 1 and 2 show perspective and front views,
respectively, of a multi-chamber microdevice 100. FIG. 3 shows a
top view of a device mold 300 used to cast the multi-chamber
microdevice 100. FIG. 4 shows a cross sectional view of device mold
300 along a plane 8 in FIG. 3.
[0063] Referring to FIGS. 1-4, multi-chamber microdevice 100 is
cast from the device mold 300. Device mold 300 is formed by
assembling a mold body 301 with two castable mold components (210
and 310), and four elongated mold components (302a, 302b, 302c, and
302d). Liquid polymer is poured into a space 304 formed between
mold body 301 and the mold components (210, 310, 302a-302d). When
the liquid polymer is cured, the elongated mold components
(302a-302d) are pulled out from the device mold 300.
[0064] In one example, the castable mold components are made of
reversible materials. Device mold 300 is heated so that the
reversible material melts into liquid state. The melted reversible
materials can be removed from the microdevice 100 by vacuum suction
or by applying a centrifugal force. Pressurized liquid or gas may
also be used to flush out the melted reversible materials.
[0065] In another example, the castable mold components are made of
sublimable materials. Microdevice 100 is heated to a sublimating
temperature of the mold components so that the sublimable material
evaporates and is separated from the microdevice 100.
[0066] In yet another example, the castabable mold components are
made of soluble materials. A solvent can be used to flush the mold
components so that the mold components dissolve in the solvent,
which is removed by suction.
[0067] In the above examples, when the mold components are removed,
an upper chamber 102, a lower chamber 103, and channels 104a, 104b,
105a, and 105b are formed in multi-chamber microdevice 100.
Microdevice 100 is subsequently released from the mold body
301.
[0068] Mold body 301 can be made of steel or plastic.
[0069] Examples of liquid polymers are polyurethane,
polydimethylsiloxane (PDMS), polycarbonate, polypyrrole, resin,
Teflon resin, epoxy, polymeric rubber, or polymeric plastic. Liquid
polymers can be solidified by mixing a polymer base and a curing
agent at a certain ratio, for example, 10:1 for PDMS mixing. The
polymerization time is about several hours at a certain
temperature. For example, the polymerization time is 48 hours at
room temperature, and 20 minutes at 100.degree. C. for Sylgard 184
Silicone Elastomer from Dow Corning. After polymerization, the
liquid polymer solidifies and forms a microstructure having
features that accurately reproduces features of the device mold
300.
[0070] Fillers or reinforcement particles can be added to the
liquid polymers to modify the properties of the solidified polymer.
The properties that can be modified by the addition of fillers or
reinforcement particles include hardness, density, impact strength,
melting temperature, chemical resistance, and abrasion resistance,
thermal conductivity, electrical conductivity, and electromagnetic
interference shielding.
[0071] Referring to FIG. 4, device mold 300 is formed by assembling
mold body 301 with mold components 210, 310, 302a-302d, 312a, and
312b. Mold components 210 and 310 define the shape of upper chamber
102 and lower chamber 103, respectively. Mold component 210 is
supported by mold members 302a and 302b at a predefined position
relative to mold body 301. Mold component 310 is supported by mold
members 302c and 302d at a predefined position relative to mold
body 301. Mold components 302a and 302b have elongated shapes
(e.g., like rods) and define the shapes of channels 104a and 104b,
respectively. Mold components 302c and 302d have elongated shapes
(e.g., like rods) and define the shapes of channels 105a and 105b,
respectively.
[0072] A portion 320 of mold component 302a is inserted through a
hole 303a formed in a sidewall 306 of mold body 301. An end 322 of
mold component 302a is inserted into a recessed structure 212a of
mold component 210. Mold components 302b-302d are connected to mold
body 301 and mold components 210 and 310 in like manner. A set rod
312a is inserted through a hole 314a of mold body 301, a hole 316
of mold component 302a, and a hole 318 of mold component 302c. Rod
312a prevents mold components 302a and 302c from moving relative to
body mold 301. Likewise, a set rod 312b prevents mold components
302b and 302d from moving relative to body mold 301. Recess
structure 212a has a ridge structure 214a, and the end 322 of mold
component 302a has a groove structure 206a that is complementary of
the ridge structure 214a. Ridge structure 214a and groove structure
206a prevent mold components 210 and 302a from moving relative to
one another. Similar structures prevent mold components 210 and
302b; and mold components 310, 302c, and 302d from moving relative
to one another.
[0073] In one example, mold components 210, 310, and 302a-302d are
all made of reversible materials. Rods 312a and 312b may be made of
the same material as mold body 301. After liquid polymer is poured
into device mold 300 and cured, rods 312a and 312b are pulled away
from device mold. The mold components are melted and removed by
suction. In this example, mold components 302a-302d can have
bending or winding shapes (e.g., such as shapes having multiple
U-turns), as long as they are sufficiently rigid to support mold
components 210 and 310.
[0074] In another example, mold components 310 and 210 are made of
reversible, soluble, or sublimable materials, while mold components
302a-302d and the rods 312a and 312b are made of the same material
as mold body 301 (e.g., steel or plastic). After liquid polymer is
poured into device mold 300 and cured, rods 312a and 312b are
pulled away from device mold 300. Then, mold components 302a-302d
are pulled away from device mold 300, forming channels 104a, 104b,
105b, and 105b. Mold components 310 and 210 are dissolved by a
solvent or removed by changing the environment conditions so that
castable mold components 210 and 310 change to liquid or vapor
state. In this example, mold components 302a-302d are straight or
curved with a constant curvature so that mold components 302a-302d
may be pulled out of device mold 300 after the liquid polymer is
cured.
[0075] To remove the mold components made of reversible materials,
after the mold components are melted and change into liquid state,
vacuum suction can be applied removed the melted component. A
centrifugal process may also be applied to remove the melted
components.
[0076] A space 308 between mold components 210 and 310 defines a
thin membrane 106 between upper chamber 102 and lower chamber 103.
Mold components 210 and 310 are positioned relative to one another
so that the thin membrane 106 is flexible. When pressurized air is
pumped into upper chamber 102, upper chamber 102 expands by pushing
thin membrane 106 downwards. If lower chamber 103 contains liquid,
then the downward movement of thin membrane 106 will push the
liquid out of the lower chamber 103. Multi-chamber microdevice 100
can be used as an air-driven liquid valve or a component of a
peristaltic micropump.
[0077] The example shown in FIGS. 1-4 uses two elongated mold
components 302a and 302b to support mold component 210. In an
alternative example, only one elongated mold component 302a is used
to support mold component 210. In the latter case, when
multi-chamber microdevice 100 is cast, only one channel (e.g.,
104a) is connected to chamber 102.
[0078] Referring to FIG. 5, mold component 210 includes recess
structures 212a and 212b for receiving the ends of mold components
302a and 302b, respectively. Ridge structures 214a (214b) prevents
mold component 210 from moving relative to mold component 302a
(302b).
[0079] FIGS. 6-8 shows a process for fabricating mold component
210. FIG. 6 shows a top view of a component mold 200 that is used
to cast mold component 210 (FIG. 5). FIG. 7 shows a cross section
of component mold 200, where the cross section is along a plane 7
that is perpendicular to the plane of FIG. 6. FIG. 8 shows a cross
section of component mold 200, where the cross section is along a
plane 8 that is perpendicular to the plane of FIG. 6.
[0080] Referring to FIGS. 6-8, component mold 200 is formed by
assembling a mold body 201, mold components 204a and 204b, and a
mold cover 208. Mold components 204a and 204b have elongated shapes
(e.g., like rods). Mold body 201 includes two holes 203a and 203b,
that allows mold components 204a and 204b, respectively, to pass
through. Mold body 201, mold cover 208, and mold components 204a
and 204b in combination form an enclosed space 202 that defines the
shape of mold component 210. Component mold 200 has an inner
surface 222 that defines the shape of a bottom surface 215 of mold
component 210 (FIG. 5). Inner surfaces 220 define the shape of side
surfaces 211 of mold component 210. Inner surface 224 define the
shape of a top surface 217 of mold component 210.
[0081] Mold body 201 has a ridge structure 206a protruding into
hole 203a. Mold component 204a has an indent structure 206b that
runs lengthwise of mold component 204a, and has a shape such that
indent structure 206b fits snugly with ridge structure 206a so as
to prevent mold component 204a from moving relative to the castable
mold component 210. Similar structures are used to prevent mold
component 204b from moving relative to mold body 201. The portion
of indent structure 206b on mold component 204a that is exposed in
space 202 defines the shape of the ridge structure 214a of the
castable mold component 210. Similar structures on mold component
204b define the ridge structure 214b of the castable mold component
210. Mold body 201, mold cover 208, and mold components 204a and
204b can be made of steel, silicon, or plastic, and can be
fabricated using, for example, microfabrication or sterolithography
techniques.
[0082] Device mold 200 may have two openings, such as holes 205a
and 205b on the mold cover 208 that connect space 202 to an
exterior of device mold 200. When a reversible material is used to
fabricate mold component 210, the reversible material can be heated
into liquid state and poured or injected into the space 202 through
the one of the openings. The temperature is lowered so that the
reversible material solidifies into mold component 210. When a
sublimable material is used to fabricate mold component 210, the
sublimable material (in powder form) can be compressed into space
202 through one of the openings. Cover 208, mold components 204a
and 204b are removed from mold component 210. Mold component 210 is
released from mold body 201.
[0083] In an alternative example, where pour casting techniques are
used, component mold 200 may have an open top, and cover 208 is not
used. In yet another example, where die casting techniques are
used, component mold 200 can be a two-piece structure (mold body
201 and cover 208).
[0084] Mold component 210 retains its dimensions after being cast
from the component mold 200. Usually, there is little change in
geometry of the mold component 210 as a result of the
solidification. This means that the size of space 202 in component
mold 200 can be made substantially the same as the desired size of
upper chamber 102. If mold component 210 is made of a material such
that the dimensions of mold component 210 changes (e.g., shrinks)
after the material solidifies, component mold 200 may be designed
so that the space 202 is slightly larger than the desired size of
upper chamber 102 to compensate for the change in dimensions during
solidification of the material. If mold component 210 is made of a
reversible material, then after multi-chamber microdevice 100 is
cast and mold component 210 is melted, the melted material may be
reused to cast other mold components.
[0085] FIG. 9 shows a multi-channel microdevice 400. FIG. 10 shows
a top view of a device mold 410 for casting the multi-channel
microdevice 400. FIG. 11 shows a cross sectional view of device
mold 410, where the cross section is along a plane 11 that is
perpendicular to the plane of FIG. 10. FIG. 12 shows a cross
sectional view of device mold 410, where the cross section is along
a plane 12 that is perpendicular to the plane of FIG. 10.
[0086] Referring to FIG. 9, a multi-channel microdevice 400
includes a separation channel 402, an injection channel 403, and
embedded reservoirs 406a, 406b, 407a, and 407b. The diameter of
channel 403 is larger than the diameter of channel 402. Channels
402 and 403 intersect at an intersection 404. Multi-channel
microdevice 400 can be used in electrophoresis. Electrodes can be
connected to embedded reservoirs 406a, 406b, 407a, and 407b from
their top openings. By applying voltages to the electrodes inserted
into the reservoirs 406a and 406b, charged particles move from the
reservoir 406a to the reservoir 406b. When a voltage difference is
applied to electrodes inserted into reservoirs 407a and 407b, a
plug of the particles at the intersection 404 moves toward the
reservoir 407b. Particles with different charge or weight will move
at different speeds along channel 402, and thus can be separated
and analyzed.
[0087] Referring to FIGS. 10-12, device mold 410 is assembled from
a mold body 429 and various mold components. Mold body 429 includes
mold base 422 and sidewalls 420a-420d. Mold base 422 includes posts
412a, 412b, 414a, and 414b, which define the shapes of embedded
reservoirs 406a, 406b, 407a, and 407b, respectively, in
multi-channel microdevice 400. The mold components include wires
416 and 418, which define the shapes of injection channel 403 and
separation channel 402, respectively.
[0088] Sidewalls 420a and 420b have holes 421a and 421b,
respectively, that allow wire 416 to pass through. Sidewalls 420c
and 420d have holes 424a and 424b, respectively, that allow wire
418 to pass through. Posts 412a and 412b have holes 426a and 426b,
respectively, that allow the wire 416 to pass through. Posts 414a
and 414b have holes 430a and 430b, respectively, that allow wire
418 to pass through. Wire 416 includes a hole 428 that allow wire
418 to pass through. Device mold 410 includes slots 432a-432d for
mold releasing.
[0089] In one example, wire 416 has a diameter of 100 .mu.m, and
wire 418 has a diameter of 200 .mu.m. This cause separation channel
402 to have a diameter of 100 .mu.m, and injection channel 403 to
have a diameter of 200 .mu.m.
[0090] Device mold 410 is assembled by connecting sidewalls
420a-420d on the mold base 422, pulling wire 416 through holes
421a, 426a, 426b, and 421b, and pulling wire 418 through holes
424a, 430a, 428, 430b, and 424b.
[0091] After device mold 410 is assembled, a liquid polymer is
poured into a region 411 defined by mold body 429 (including mold
base 422 and sidewalls 420a-420d) and the mold components
(including wires 416 and 418, and posts 412a, 412b, 414a, and
414b). The liquid polymer cures or solidifies in device mold 410.
After the liquid polymer is cured, wire 418 is pulled out, leaving
a space that becomes the separation channel 402. Wire 416 is pulled
out, leaving a space that becomes the injection channel 403. The
fabricated multi-channel microdevice 400 is released from device
mold 410 and turned over with the openings of embedded reservoirs
406a, 406b, 407a, and 407b on the top.
[0092] Portions 408 of channel 403 that extend from reservoirs 406a
and 406b to sidewalls 405d and 405b, respectively, of microdevice
400 can be used to deliver fluid into channels 403 and 402, or be
sealed by glue. Likewise, portions 409 of channel 402 that extend
from reservoirs 407a and 407b to sidewalls 405c and 405b,
respectively, of microdevice 400 can be used to deliver fluid into
channel 402 and 403, or be sealed by glue
[0093] For example, wires 416 and 418 can be steel wires, glass
fibers, carbon fibers, or aramid fibers. Wires 416 and 418 can be
straight or have constant curvatures so that the wires can be
pulled out of device mold 410. The diameters of the wires 416 and
418 are selected to be substantially the same as the desired
diameters of channels 403 and 402, respectively. The diameters of
wires 416 and 418 can range from nanometers to micrometers,
depending upon the application. Reversible, sublimable, and soluble
materials can also be used to create wires 416 and 418.
[0094] The techniques for fabricating multi-chamber microdevice 100
and multi-channel microdevice 400 can be used to fabricate
microstructures in a microfluidic device. Other microdevices, such
as microsensors, may also be fabricated using similar techniques.
Medical microdevices can also be achieved in biomedical
applications. Such microdevices can include implantable microsystem
for medical diagnostics or drug delivery.
[0095] Referring to FIGS. 13-15, an integrated microfluidic system
900 that may be used in DNA analysis includes a microfluidic device
500, and a cassette 800. Microfluidic device 500 includes a
microdevice body 501 having predefined structures that form
microfluidic components and an integrated platform 600 having
functional components mounted thereon. To fabricate microdevice
body 501, a device mold is constructed by assembling a mold body,
platform 600, and various mold components. Some or all of the mold
components can be made of reversible, sublimable, or soluble
materials.
[0096] Microdevice body 501 is cast from the device mold by pouring
liquid polymer into the device mold and curing the liquid polymer
so that it solidifies. Techniques for removing mold components from
device molds 300 and 410 can be used to remove the mold components
from the device mold for fabricating microdevice body 501. The
microfluidic device 500 is then released from the mold body. In one
example, platform 600 includes an integrated circuit board 620
having functional components soldered to the circuit board 620.
[0097] Microfluidic device 500 includes fluidic parts, such as a
sample loading reservoir 526 (FIG. 17), a polymerase chain reaction
(PCR) chamber 524, a peristaltic micropump 517 (FIG. 18), chambers
for a microvalve 516 (FIG. 19), a separation channel 504, an
injection channel 508, fluidic interfaces 514a-514d, and a
pneumatic interface 518a (FIG. 14).
[0098] Microfluidic device 500 includes detection and controlling
parts, such as circuit board 620, a laser diode 530, a microlens
532, an integrated circuit 536, a microheater 522, a thermal sensor
528, electrodes 512a-512d, an electrode set 534, a ring microheater
604, a domed diaphragm 602 made of shape memory alloy, and
connection pins 506. Thermal sensor 528 is integrated inside PCR
chamber 524, and microheater 522 is placed beneath PCR chamber 524.
Connection pins 506 provides electrical interfaces for various
electronic components, such as laser diode 530, microheater 522,
thermo sensor 528, electrode set 534, microheater 604, and
electrodes 512a-512d. Light waveguides 502 and 503 (FIG. 24) for
fluorescence emission detection is also integrated inside the
microdevice body 501.
[0099] Cassette 800 (FIGS. 13 and 25) includes a bottom wall 801a
and sidewalls 801b. The bottom wall 801a has electrical sockets 802
for interfacing the connection pins 506 in the microfluidic device
500. The sidewalls 801b have pneumatic interfaces 814a-814c for
interfacing micropump 517, fluidic interfaces 812a-812d for
supplying liquid to the interfaces 514a-514d on the sides of
microfluidic device 500, electrical interfaces 808 and 810 for
interfacing electrical components connected to electrical sockets
802, and a photo sensor 804 for detecting light signals.
[0100] The following describes a process for conducting DNA
analysis using microfluidic system 900.
[0101] A running buffer is loaded from the fluidic interface 514c
into the microfluidic device 500 filling all the chambers and
channels. A sample containing DNA fragments is injected by a
pipette into sample loading reservoir 526. The pump 517 operates to
pump the sample from sample loading reservoir 526 to PCR chamber
524 through a channel 521a. The sample in PCR chamber is
thermocycled by microheater 522, and the temperature of the sample
is measured by microsensor 528. Microheater 522 and microsensor 528
are connected to integrated circuit 536, which controls the
microheater 522 to adjust the temperature of PCR chamber to
facilitate the multiplication of DNA segments. Then the sample is
pumped to a chamber 710 of a microvalve 516 using peristaltic
micropump 517. Micropump 517 includes three sub-pumps 513. Each
sub-pump 513 includes a pneumatic interface (e.g., 518a), an air
chamber (e.g., 519a), and a liquid chamber (e.g., 520a). The
pneumatic interfaces 518a-518c are connected to pneumatic
interfaces 814a-814c on the cassette 800 and then to a source that
supplies pressurized air (not shown).
[0102] Detail of microvalve 516 is shown in FIG. 19. The chamber
710 is connected to an embedded reservoir 510b through an injection
channel 508. An embedded reservoir 510a is connected to another
embedded reservoir 510c through a separation channel 504. Injection
channel 508 and separation channel 504 are connected at an
intersection 505. Electrodes 512a-512d are integrated with embedded
reservoirs 510a-510c band chamber 710, respectively. Applying a
voltage (e.g., 300 V) across electrodes 512d and 512b generates an
electro-osmotic (or electrophoretic) flow that causes the sample in
chamber 710 to flow through injection channel 508 towards embedded
chamber 510b. Applying a voltage (e.g., 1000 V) across electrodes
512a and 512c generates an electro-osmotic (or electrophoretic)
flow that causes a plug of the sample at the intersection 505 to
flow from intersection 505 towards embedded reservoir 510c, thereby
separating the DNA fragments in the fluid along the length of
separation channel 504 according to their weight and charge.
[0103] The DNA fragments are detected by a technique called
capillary electrophoresis, in which laser-induced fluorescence
detection is used. As the fluid containing DNA fragments flow
through a detection region 529 of separation channel 504, the DNA
fragments are illuminated by a laser beam emitted from diode laser
530. A microlens 532 focuses the laser beam onto detection region
529. In an alternative setup, an external laser can be used with a
mirror or a waveguide integrated inside microfluidic system 900 at
the position of the laser diode 530 to deliver the laser beam from
the external laser to detection region 529. The DNA fragments are
bonded with fluorescent tags, which produce fluorescence emission
when excited by the laser beam.
[0104] An O-shaped optical waveguide conduit 503 directs emission
scattered from the DNA fragments towards an optical waveguide 502,
which guides the fluorescence emission to the photo sensor 804 in
the cassette 800. By analyzing the signals detected by photo sensor
804, it is possible to determine the type of fluorescent tags
passing through detection region 529, hence determining the type of
DNA fragments in the fluid. Capillary electrophoresis performed by
using system 900 allows rapid, high-resolution, and high
sensitivity detection of the DNA fragments.
[0105] The DNA fragments can also be detected using a technique
called electrochemical detection, which can monitor small volumes
of the DNA fragments separated inside separation channel 504. A set
of electrochemical electrodes 534 reacts with DNA fragments that
pass through a detection region 535 of separation channel 504.
During the reaction, electrons are gained or lost at the electrode,
which generates electrical signals that can be processed by
integrated circuit 536.
[0106] The set of electrochemical electrodes 534 includes three
electrodes (FIG. 22): a working electrode 756, a reference
electrode 754, and a counter electrode 752. Electrodes 754 and 756
are embedded in microdevice body 501, and have tips that are
ring-shaped (FIG. 23). The ring-shaped tips have inner diameters
the same as the diameter of the channel 504. The surface of the
ring-shaped tips of electrodes 754 and 756 form part of the surface
of channel 504. Channel 504 is connected to a cone-shaped chamber
750, which is connected to embedded reservoir 510c. Electrode 752
is a tip electrode that extends into cone chamber 750 and contacts
the fluid flowing in cone chamber 750. The set of electrochemical
electrodes 534 are mounted on circuit board 620 and connected to
integrated circuit 536, which amplifies and processes signals
detected by the set of electrodes 534.
[0107] In one example, segments (e.g., 515a-515c) of channels from
the reservoirs to the sidewalls of the microdevice body 501 can be
used as interfaces to connect channels 504 and 508 to an exterior
of microfluidic device 500. The segments 515a-515c of channels can
be used for injecting or removing liquid from channels 504 and 508,
such as when cleaning channels 504 and 508. In another example, the
segments 515a-515c of channels can be used to couple microfluidic
device 500 to other systems, such as the cassette 800. In yet
another example, the segments 515a-515c of channels may be sealed
after the microdevice body 501 is released from the mold body.
[0108] FIG. 15 shows a perspective view of integrated platform 600.
The platform 600 includes a circuit board 620, on which electrical
and optical components are mounted.
[0109] Referring to FIG. 16, a process 910 is used to fabricate
microstructures inside a solid body by using micro-mold components
to define the microstructures. Process 910 includes the following
steps:
[0110] Step 31: Fabricating component molds. Component mold 200 is
fabricated to cast mold components 210, which are used to define
the air chambers 519a-519c of micropump 517. Another component mold
is fabricated to cast mold components 310, which are used to define
the liquid chambers 520 of micropump 517. Similarly, other
component molds are fabricated or assembled to cast additional mold
components that are used to define additional microstructures in
microdevice body 501.
[0111] Step 32: Casting mold components. Reversible, sublimable, or
soluble materials are poured, injected, or compressed into the
component molds fabricated or assembled in step 31. After the
material solidifies, the mold components are separated from the
component molds.
[0112] Step 33: Fabricating and assembling the device mold. A
device mold for casting microdevice body 501 is assembled using a
mold body, various mold components, and the integrated platform
600. For example, mold components 210 and 310 may be used to define
the shapes of chambers 519a and 520a, respectively, of micropump
517. Wires 416 and 418 may be used to define the shapes of
injection channel 508 and separation channel 504, respectively. A
mold component 742 (FIG. 21) may be used to define the shapes of
embedded reservoirs 510a-510c. The device mold can be open on
the-top for pour casting, or be a closed structure for injection
casting.
[0113] Step 34: Coating the surfaces of the mold device, including
the mold body and mold components, with a mold release agent. This
step may be omitted when liquid polymer is used for casting the
microdevice body and the microdevice body does not adhere to the
mold body and mold components.
[0114] Step 35: Casting the microstructure body. Liquid polymer is
poured or injected into the device mold to fill in the space
defined by the mold body and the mold components. The liquid
polymer is selected so that its melting temperature is lower than
the melting (or sublimation) temperature of the mold
components.
[0115] Step 36: Removing the mold components from the
microstructure body 501. Where mold components (e.g., 210 and 310)
are supported by rods (e.g., 302a-302d), these rods are melted or
pulled away from the device mold. Removing the rods create channels
in the microdevice body 501. These channels provide access for
removing the mold components (e.g., 210 and 310) from the
microdevice body 501. The mold components may be heated so that
they melt (or vaporize), or a solvent may be used to dissolve the
mold components. The melted or dissolved mold components are
removed by use of vacuum suction force or centrifugal force.
[0116] Step 37: Releasing the microdevice body 501 from the mold
body.
[0117] An advantage of using microfluidic system 900 is to
eliminate off-line sample processing. This is accomplished by
integration of sample and reagent handling, reaction, and detection
within a single microfluidic system 900. Microfluidic system 900
allows electrophoretic analysis, including fluidic handling,
polymerase chain reaction, laser-induced-fluorescence detection,
and electrochemical detection to be performed on a single
integrated device.
[0118] In the example of microfluidic system 900, there are eight
functional parts that are integrated: (1) the sample loading
reservoir 526; (2) the PCR chamber 524, the microheater 522, and
thermal sensor 528; (3) the three-stage peristaltic micropump 517;
(4) the microvalve 516; (5) the microchannels 504 and 508 for
separation analysis; (6) the electrodes 510a-d for voltage
application; (7) the LIF detection by laser diode 530, microlens
532, waveguides 503 and 502, optical filter 806, and photo sensor
804; (8) the electrochemical detection by electrode set 534 and its
appropriate electronics 536.
[0119] Referring to FIG. 17, sample loading reservoir 526 includes
a fluidic chamber 704, an inlet channel 521c, an outlet channel
521a, and a V-shape funnel 702 connected to fluidic chamber 704
through a funnel tip 700. Outlet channel 521a connects to the PCR
chamber 524 (FIG. 18). When loading a sample, a tip of a pipette
having the sample is pushed through the V-shape funnel 702 and
funnel tip 700. After the sample is transferred from the pipette to
fluidic chamber 704, the sample is pumped to the PCR chamber 524
(FIG. 18) through channel 521a.
[0120] When flushing the channels and the chambers using a liquid,
the liquid flows from inlet channel 521c into chamber 704 and to
outlet channel 521a. Funnel tip 700 is designed to have a thin
flexible wall 703 and a small opening 701. Opening 701 opens when a
pipette tip is pushed through funnel tip 700 in a direction from
V-shape funnel 702 to chamber 704. When liquid is flushed into
chamber 704 from inlet channel 521c, the pressure of the flushing
liquid squeeze the thin wall 703 of the funnel tip 700 so that
opening 701 is closed. This prevents the flushing liquid from
flowing out through the funnel 702.
[0121] PCR chamber 524, and air chambers 519a-519c, and liquid
chambers 520a-520c of the micropump 517 can be created by mold
components that are similar to mold component 210 depicted in FIG.
5. An elongated mold component, such as a small wire or a rod, can
be used to pass through and string together the mold components for
the PCR chamber 524 and micropump 517. After microdevice body 501
is cast and cured, the elongated members, such as the wires, rods,
or sheets, are pulled out to create channels, such as 521a- 521d,
that connects the chamber 704 of sample loading reservoir 526, PCR
chamber 524, micropump 517, and microvalve 516. Three elongated
mold components, such as rods or sticks, support the three mold
components for defining the three air chambers 519a-519c. After
microdevice body 501 is cast and cured, the elongated members are
pulled out to create pneumatic interfaces 518a-518c.
[0122] Referring to FIG. 18, peristaltic micropump 517 is operated
using four-stage cycles: Stage 1 (519a-D, 519b-D,
519c-I).fwdarw.stage 2 (519a-I, 519b-D, 519c-D).fwdarw.stage 3
(519a-I, 519b-I, 519c-D).fwdarw.stage 4 (519a-D, 519b-I, 519c-I),
where D means deflated, and I means inflated.
[0123] Referring to FIG. 19, microvalve 516 is actuated by using a
domed diaphragm 602 made by shape memory alloy (SMA) surrounded by
a ring microheater 604. Domed diaphragm 602 has small holes 716.
Electrical connections (not shown) connect ring microheater 604 to
printed circuit board (PCB) 620. Microvalve 516 includes a lower
chamber 710 that connects a channel 521d from chamber 520c of
micropump 517. Microvalve includes an upper chamber 718, an
interconnecting channel 712, and a top vent 714.
[0124] At the bottom of chamber 710, there is an electrode plate
512d, connected to a lead 722, which is soldered to the PCB 620.
Electrode plate 512d is used to apply a voltage to the fluid in
chamber 710.
[0125] Microvalve 516 operates in two states: an open state and a
closed state. To operate microvalve 516 in the closed state,
electric current is applied to ring microheater 604 to heat
diaphragm 602. This causes diaphragm 602 to curve downwards, as
shown in dished line 715, such that a center portion 713 of
diaphragm 602 seals the channel 712 connecting upper chamber 718 to
lower chamber 710. To operate microvalve 516 in the open state, the
electric current is not applied to ring microheater 604, causing
diaphragm 602 to cool and to restore to its normal shape, which has
a shape that curves upwards, as shown in solid lines. This allows
fluid or air to flow freely from lower chamber 710 to upper chamber
718 through interconnecting channel 712, and from upper chamber 718
to top vent 714 through holes 716.
[0126] Microvalve 516 is typically operated in its open state when
a sample is pumped from the sample loading reservoir 526 to PCR
chamber 524 and from PCR chamber 524 to lower chamber 710.
Microvalve 516 is typically operated in its closed state for buffer
loading or channel flushing when liquid is pumped from fluidic
interface 514c to PCR chamber 524, liquid chambers 520a-520c, lower
chamber 710, then to injection channel 508 and separation channel
504. The buffer fluid or flushing fluid is pumped out of
microfluidic device 500 through fluidic interfaces 514a,. 514b, and
514d.
[0127] Microvalve 516, with its SMA domed diaphragm 602 and ring
microheater 604, shows an example of mechanical integration within
a microfluidic device 500. Microvalve 516 can be replaced by a
pressure-air-driven close-and-open structure having an upper
chamber and a lower chamber, similar to chambers 519a and 520a of
micropump 517, with a thin membrane 106 in between the upper and
lower chambers. The microvalve is closed when pressured air is
supplied to the upper chamber 519a, causing the thin film to flex
downward to close interconnecting channel 712. The microvalve is
opened when the pressured air is released from the upper channel,
causing the thin film to return to its normal position, opening
interconnecting channel 712.
[0128] Referring to FIG. 20, an embedded reservoir 510a is
integrated with electrode 512a. Similarly, embedded reservoirs 510b
and 510c are integrated with electrodes 512b and 512c,
respectively. Electrode 512d is integrated with chamber 710 of
microvalve 516. The electrodes are positioned below embedded
reservoirs 510a-510c and chamber 710.
[0129] Because channels 504 and 508 have small diameters, it may be
difficult to remove melted or dissolved mold components from
channels having the same diameters as channels 504 or 508. Thus, an
enlarged channel 515a is created to connect reservoir 510a to
fluidic interface 514a at a sidewall of microdevice body 501.
[0130] Referring to FIG. 21, to create the structure shown in FIG.
20, a device mold 920 is assembled by connecting a mold component
742, electrode 512a, a part of printed circuit board 620, a wire
746, a solid tubing 744, and a mold body 740. Mold component 742
has a shape that is the same as a shape of embedded reservoir 510a.
Solid tubing 744 has an inner diameter that is the same as a
diameter of wire 746. Solid tubing 744 and wire 746 are pulled
through a hole 748 on mold body 740. Wire 746 is threaded through
tubing 744, and strings together mold component 742 and other mold
components. Tubing 744 is partly inserted into mold component 742.
After casting the microdevice body 501, wire 746 is pulled out from
body 501 through tubing 744, creating channel 504. Tubing 744 is
pulled out of hole 748, creating channel 515a, which has a diameter
larger than channel 504. Having made channel 515a, mold component
742 can be easily removed from the microdevice body 501 to create
chamber 510a.
[0131] Referring to FIGS. 22 and 23, an electrode set 534 includes
two in-channel ring electrodes 754 and 756, and an end-channel
electrode 752. The electrode set 534 is used to perform
electrochemical detection at the end of the separation channel 504.
Electrode set 534 includes a working electrode 756, a reference
electrode 754, and a counter electrode 752. Electrodes 756 and 754
are ring shaped and surround separation channel 504. Portions of
electrodes 756 and 754 contact the fluid flowing in channel 504.
FIG. 23 shows a more detailed view of electrode 756 with the
channel 504. These two electrodes 754 and 756 create an electrical
signal that is dependent on chemical constituents of the fluid in
channel 504 during separation analysis. Counter electrode 752 has a
pointed tip electrode that extends into a cone chamber 750 that
connects chamber 510c and channel 504. Leads 534a, 534b, and 534c
serve as posts that connect electrodes 752, 754, and 756,
respectively, to PCB 620 and to integrated circuit 536 for signal
amplification and processing.
[0132] The following describes a processing for integrating
electrodes 752-756 with microdevice body 501. Electrodes 752-756
and their leads 534a-534c are assembled on PCB 620 and positioned
so that the center holes of the ring electrodes 754 and 756 and the
tip of the electrode 762 are at the same level as the microchannel
504. A wire 746 is pulled through the center holes of the ring
shaped electrodes 754 and 756. The tip of the wire is inserted into
a cone shaped mold component that is used to create the cone shape
chamber 750 and reservoir 510c. Electrode 752 is wedged inside the
cone shaped mold component. After casting microdevice body 501,
wire 746 is pulled out, and the mold components are removed from
microdevice device 501. Electrodes 752, 754, and 756 become
embedded inside the microdevice device 501 at proper positions
suitable for electrochemical detection.
[0133] Referring to FIG. 24, light induced fluorescence detection
is performed by using laser diode 530, microlens 532, O-shape
optical waveguide 503, and optical waveguide 502. Microlens 532 is
supported by a holder 760. Laser diode 530 generates a laser beam
to excite molecules labeled with fluorescent tags in the sample. To
gather fluorescence emission, the O-shape optical waveguide 503 is
designed to surround channel 504. Microlens 532 focuses the laser
beam into the channel 504 through a small opening 762 on the
O-shape waveguide 503. If the intensity or the wavelength of the
laser diode 530 is not suited for the excitation, a mirror can be
integrated at the position of the laser diode 530 to bend the
external laser beam from the underneath of the microfluidic device
500. The laser beam can also be directly focused on channel 504
with an external focus lens positioned below channel 504. In the
latter example, the hole 762 can be made at the bottom of the
O-shape optical waveguide 503. A hole having a size approximately
the same as hole 762 is also created on the circuit board 620 to
allow the laser beam to pass through.
[0134] Optical waveguides 502 and 503 gather and deliver light from
channel 504 to the photo sensor 804. Using the microfabrication
techniques described herein, an optical waveguide can be integrated
into a microdevice by creating a conduit with a certain shape and
filling it with an appropriate liquid. The liquid has a refractive
index greater than that of the microdevice material. Waveguide 502
transmits the fluorescent emission to an optical filter 806 then to
a photo sensor 804 (FIG. 25). The inside wall of the waveguide
conduit 502 and 503 may be coated with a material, such as Teflon
AF resin, whose refractive index is less than a transparent liquid
that is filled into the conduit. In this way, a liquid core
waveguide can be created.
[0135] FIG. 25 shows a top view of cassette 800 that can be coupled
to microfluidic device 500. Cassette 800 includes three adapters
814a-814c positioned on a sidewall 801. Adapters 814a-814c
correspond to the pneumatic interfaces 518a-518c of micropump 517.
Fluidic adapters 812a-812d (which are built on sidewalls of
cassette 800) correspond to fluidic interfaces 514a-514d,
respectively, of microfluidic device 500. Each adapter has an
o-ring groove (e.g., 816) for fitting an O-ring seal to prevent
leakage of pressurized air or liquid.
[0136] Electrical sockets 802 are provided at the bottom wall 801 a
of cassette 800 to receive interface pins 506 of microfluidic
device 500. Sockets 802 are connected to electrical interfaces 808
and 810 built on the sidewalls of cassette 800. Interface 810 can
be used for high voltage connection (e.g., used to apply voltages
to electrodes 512a-512d), and interface 808 can be used for various
measurement and controlling signals.
[0137] Photo sensor 804 is mounted on a sidewall of cassette 800
for photo detection. Optical filter 806 is used to block the
excitation and the scattering light, and to pass the emission
wavelength from the sample excited by the laser in the separation
channel 504. Four setscrews 818 are provided at four corners of
cassette 800 to allow cassette 800 to be assembled with other
components, or be secured on a support frame. Cassette 800 can
serve as an interface between the microfluidic device 500 and
external components with a convenient "plug-and-play" design. A
component that cannot fit within microfluidic device 500 (e.g., due
to its size, cost, or compatibility) can be placed in cassette 800.
Such components may include a microprocessor, a high power laser
source, a photo sensor, and additional optical parts. The cassette
structure provides an easy way for microstructure interfacing with
structures that can be more easily handled by a user, and makes the
detections and controls as close as possible to the microstructure,
so that detection signal loss due to transmission is decreased as
less as possible and the microsystem performance is increased.
[0138] Integrated microfluidic system 900 allows miniaturization of
chemical, biological, and medical analytical systems. An advantage
of using microfluidic system 900 is that smaller sample and reagent
volumes are required, better system portability and disposability.
Another advantage is that the microstructures of microfluidic
system 900 are fabricated by casting liquid polymers or resins. It
is not necessary to use bonding procedures that were used in
traditional microfabrication methods. By using casting techniques,
microstructures having a variety of shapes and sizes can be
achieved. The microstructures can have features with high aspect
ratios (i.e., very narrow or small in one dimension as compared to
another dimension). The microdevice body 501 can be fabricated as a
single structure. There is no liquid leakage from the device and
between the microstructures inside the device, as may occur if the
microstructure body 501 was fabricated by binding different
components. Using casting techniques to fabricate microdevice body
501 increases the quality and reliability of the microfluidic
system 900, simplifies the fabrication process, and decreases the
product defect rate. When mass-produced, the cost of microfluidic
device 500 may be lower compared to cassette 800. Microfluidic
device 500 (which is made of polymer or resin, and can be made
cheaper) wears out earlier than cassette 800 (which can be made of
steel or plastic, and is likely more expensive). Using the
plug-and-play approach, it is possible to dispose microfluidic
device 500 after repeated usage while retaining cassette 800 for
later use.
[0139] The techniques for fabricating multi-chamber device 100 and
multi-channel device 400 can be used to fabricate complicated
Microsystems, in additional to microfluidic device 500.
[0140] Using liquid polymers and resins to fabricate microdevice
body 501 has the advantage of low cost and low toxicity. Some
polymers and resins are transparent from the visible to the near
ultraviolet wavelength, which makes them suitable for fluorescence,
chromatographic, emission, absorption, and other spectroscopic
detection. By integrating electrodes into the channels and chambers
of microdevice body 501, electrochemical detection and bioimpedance
measurements can be performed. Polymers and resins have the
advantage of chemical inertness, versatile surface chemistry, and
mechanical flexibility and durability.
[0141] The casting techniques described herein for fabricating
microstructures can be used in many different applications,
including analytical chemistry, biological diagnosis, medical
diagnosis, food testing, environment testing, biodefence, and drug
detection and screening. Microsystems incorporating microstructures
fabricated using the casting techniques can be used in microsensors
and microtransducers that are useful for industrial measurement and
control. The casting techniques can also be used to create a
variety of MEMS devices.
[0142] Although some examples have been discussed above, other
implementation and applications are also within the scope of the
following claims. For example, in FIG. 13, instead of using a photo
sensor 804 coupled to waveguide 502, an embedded photo sensor with
sufficient sensitivity can be placed near the detection region 529
to detect the fluorescence emission from fluorescent tags bound to
the DNA fragments. A lens may be required to focus the fluorescence
emission to the embedded photo sensor. Microfluidic system 900, in
addition to being used to analyze DNA fragments, can be used to
analyze other types of analytes, including proteins and
electrolytes. The DNA fragments can be combined with UV tags that
emit light when illuminated with ultraviolet (UV) light. Diode
laser 530 may emit UV light suitable for exciting the UV tags.
[0143] Fabrication of the microstructure devices using materials
that change from solid state to liquid state in response to
temperature changes may be performed under controlled environments
that have lower temperatures when casting the microstructure device
so that the mold components remain in solid state when the casting
process is performed. Some materials may be in solid state under a
particular atmospheric pressure, and in liquid or vapor state in
another atmospheric pressure. Fabrication of the microstructure
devices using such materials may be performed under controlled
environments that have a higher atmospheric pressure when casting
the microstructure device so that the mold components remain in
solid state when the casting process is performed. A material that
changes from liquid state to solid state Upon exposure to
ultraviolet light may also be used to fabricate the mold
components. Microfluidic system 900 may be used for different types
of electrophoretic analysis in additional to analyzing DNA samples.
Microfluidic system 900 may also be used for DNA microarray
analysis with an array chip integrated inside a chamber.
[0144] The method of fabricating microstructure body 501 can be
used to fabricate microstructures used in applications other than
microfluidic systems. The technique of assembling a device mold and
casting a microstructure body from the device mold can be used to
fabricate any micron scale integrated system. Accordingly, other
embodiments are within the scope of the following claims.
* * * * *